A PHASE 3, RANDOMIZED, BLINDED, PLACEBO-CONTROLLED STUDY OF TISLELIZUMAB (BGB-A317) PLUS CHEMORADIOTHERAPY FOLLOWED BY TISLELIZUMAB MONOTHERAPY IN NEWLY DIAGNOSED, STAGE III SUBJECTS WITH LOCALLY ADVANCED, UNRESECTABLE NON-SMALL CELL LUNG CANCER
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- Celgene
- 入组人数
- 1
- 试验地点
- 163
- 主要终点
- Progression-Free Survival (PFS)
研究概览
简要总结
This is a Phase 3, randomized, double-blind, placebo-controlled multicenter global study designed to compare the efficacy and safety of tislelizumab in combination with concurrent chemoradiotherapy (cCRT) followed by tislelizumab monotherapy versus cCRT alone, and tislelizumab given sequentially after cCRT versus cCRT alone, in newly diagnosed stage III subjects with locally advanced, unresectable non-small cell lung cancer (NSCLC). The primary endpoint is centrally-assessed progression free survival (PFS) in the intent-to-treat (ITT) population. .
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Newly diagnosed, histologically confirmed, locally advanced, stage III unresectable non small cell lung cancer (NSCLC).
- •Staging will be confirmed at screening by positron emission tomography-computed tomography (PET/CT) and brain imaging by magnetic resonance imaging (MRI) or computed tomography (CT) with contrast.
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤
- •Epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) gene translocation status available prior to randomization.
- •Provision of fresh or archival tumor tissue or discussion with Sponsor.
- •Adequate hematologic and end-organ function.
排除标准
- •Prior therapies including those targeting PD-1 or PD-L1 or chemotherapy, radiation, targeted therapy, biologic therapy, immunotherapy or investigational agent used to control non-small cell lung cancer (NSCLC).
- •History of severe hypersensitivity reactions to other monoclonal antibodies or any contraindication to the planned chemotherapy regimen.
- •History of, or ongoing, interstitial lung disease; pneumonitis requiring steroids; or clinically significant pericardial effusion.
- •Any active malignancy less than or equal to 2 years before randomization, with the exception of non-small cell lung cancer (NSCLC) and any locally recurring cancer that has been treated curatively.
- •Severe chronic or active infections including those requiring systemic antibacterial, antifungal or antiviral therapy; known human immunodeficiency virus (HIV) infection; untreated chronic hepatitis B or chronic hepatitis B virus carries or active hepatitis C; or active autoimmune disease.
- •Prior allogeneic stem cell transplantation or organ transplantation.
- •Significant cardiovascular disease or other condition which places the patient at risk.
研究组 & 干预措施
Arm 1:Tislelizumab + cCRT followed by tislelizumab monotherapy
Tislelizumab 200 mg is administered by intravenous (IV) administration and given together upfront with concurrent platinum-based chemoradiotherapy (cCRT) for the first 6 weeks, followed by tislelizumab 200 mg by IV adminstration monotherapy. The standard platinum-based chemotherapy options include carboplatin/ paclitaxel and cisplatin/etoposide
干预措施: Tislelizumab (Drug)
Arm 1:Tislelizumab + cCRT followed by tislelizumab monotherapy
Tislelizumab 200 mg is administered by intravenous (IV) administration and given together upfront with concurrent platinum-based chemoradiotherapy (cCRT) for the first 6 weeks, followed by tislelizumab 200 mg by IV adminstration monotherapy. The standard platinum-based chemotherapy options include carboplatin/ paclitaxel and cisplatin/etoposide
干预措施: Concurrent chemoradiotherapy (cCRT) (Drug)
Arm 2: Placebo + cCRT followed by tislelizumab monotherapy
Placebo is given with concurrent platinum-based chemoradiotherapy (cCRT) for the first 6 weeks, followed by tislelizumab 200 mg by IV administration monotherapy. The standard platinum-based chemotherapy options include carboplatin/paclitaxel and cisplatin/etoposide.
干预措施: Tislelizumab (Drug)
Arm 2: Placebo + cCRT followed by tislelizumab monotherapy
Placebo is given with concurrent platinum-based chemoradiotherapy (cCRT) for the first 6 weeks, followed by tislelizumab 200 mg by IV administration monotherapy. The standard platinum-based chemotherapy options include carboplatin/paclitaxel and cisplatin/etoposide.
干预措施: Concurrent chemoradiotherapy (cCRT) (Drug)
Arm 2: Placebo + cCRT followed by tislelizumab monotherapy
Placebo is given with concurrent platinum-based chemoradiotherapy (cCRT) for the first 6 weeks, followed by tislelizumab 200 mg by IV administration monotherapy. The standard platinum-based chemotherapy options include carboplatin/paclitaxel and cisplatin/etoposide.
干预措施: Placebo (Other)
Arm 3: Placebo + cCRT followed by placebo monotherapy
Placebo is given with concurrent platinum-based chemoradiotherapy (cCRT) for the first 6 weeks, followed by placebo monotherapy. The standard platinum-based chemotherapy options include carboplatin/paclitaxel and cisplatin/etoposide.
干预措施: Concurrent chemoradiotherapy (cCRT) (Drug)
Arm 3: Placebo + cCRT followed by placebo monotherapy
Placebo is given with concurrent platinum-based chemoradiotherapy (cCRT) for the first 6 weeks, followed by placebo monotherapy. The standard platinum-based chemotherapy options include carboplatin/paclitaxel and cisplatin/etoposide.
干预措施: Placebo (Other)
结局指标
主要结局
Progression-Free Survival (PFS)
时间窗: Up to approximately 5 years; date of randomization to the date of tumor progression or death; until study withdrawal date of 26 June 2019
Progression-free survival was defined as the time from the date of randomization to the date of the first objectively tumor progression as assessed by the blinded independent central review per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 criteria (documented by radiological assessment) or death (any cause) on or prior to the clinical cut-off date, which ever occurred first. Stable disease-neither sufficient shrinkage to qualify for PR nor sufficient increase of lesions to qualify for Progressive disease (PD)• Progressive Disease- At least a 20% increase in the sum of diameters of target lesions from nadir.
次要结局
- Overall Survival at 24 Months(Up to approximately 24 months)
- Overall Survival (OS)(Up to approximately 5 years; date of randomization to date of death from any cause.)
- Percentage of Participants Who Achieved a Best Overall Response of Complete Response or Partial Response(Up to approximately 5 years)
- Duration of Response(Up to approximately 5 years)
- Percentage of Participants Alive and Progression-Free at 12 Months (APF12)(Up to 12 months)
- Percentage of Participants Alive and Progression-free at 18 Months (APF18)(Up to approximately 18 months)
- Time to Distant Metastasis (TTDM)(Up to approximately 5 years)
- Number of Participants With Treatment Emergent Adverse Events (TEAEs)(From first dose of study drug up to study withdrawal date of 26 June 2019; 15 days.)
- Number of Participants With Lung Cancer Symptoms Assessed by the Corresponding Domains of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC-QLQ-C30) and Lung-Cancer Specific QLQ-LC13(Up to approximately 5 years)
- Percentage of Participants Who Would Have Continued on to Monotherapy Phase(Up to approximately 5 years)